Preserving Brain Health in a Toxic Age New Insights from

Neuroscience, Integrative Medicine, and Public Health

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 —adverse effects | Brain—drug effects | Environmental Exposure—
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The author of this book does not dispense any medical advice or
recommend any medical techniques or interventions. This book is a
discussion of information pertaining to scientific research and related
information regarding selected disorders as well as related historical
information. Its content does not constitute medical advice, nor should it be
construed as such. The content of this book is for general information only.
This information is not intended to be patient education, does not create any
patient-physician relationship, and should not be used as a substitute for
professional diagnosis and treatment. The author and publisher make no
warranties to readers, expressed or implied, as to the completeness or
accuracy of the material herein. The author and publisher do not assume
responsibility for readers’ actions related to any of its content.
Contents

Acknowledgments
Introduction
1 Tempering the Inflamed Brain
2 The World of Neurotoxins: Then and Now
3 Your Microbiome and Its Discontents: Implications for Brain Health
4 Fatty Liver and Brain Health: Are We Eating Ourselves toward Brain
Dysfunction?
5 The Many Facets of Dementia: Genes, Environmental Toxins,
Infectious Agents, and Other Insults
6 Can Alzheimer’s Be Avoided or Treated?
7 Autism: Developmental Disorder Early in Life
8 Acetaminophen and Autism: Neurons and Liver at Risk
9 Autonomic Nervous System Dysfunction and Chronic Fatigue
Syndrome
10 Postmodern Stress Disorder: Rewired for Violence?
11 Future of Our Brains and Their Environment in the Twenty-first
Century
12 Differing Epistemologies of Allopathic and Integrative Medicine:
Reflections on Their Strengths and Weaknesses
13 Brain Health: Summation and the Way Forward
Notes
About the Author
Acknowledgments

Great thanks are due to my highly accomplished wife, Barbara J. A. Eiser,

who has provided invaluable support and incisive editing, and to my
daughter, Arielle, who offered her insights, both having improved several
chapters. They have also graciously put up with me during the many hours
and years that I have worked on this book. I wish to give a heartfelt thanks
to my friend Bill Fuentevilla, who has helped me throughout this effort with
his keen insights, helpful editing, and much-needed encouragement.
My cousin Melvin Vigman, MD, a neurologist, provided important
observations improving this effort. My friend David Galinsky, MD, a
geriatrician, likewise brought invaluable acumen and useful editing to this
work. My friend Michael Parmer, MD, contributed helpful comments and
his literary flair as well. My friend Marc Lipsitt offered useful insights. I am
deeply grateful to all of them.
I wish to express thanks to Suzanne Staszak-Silva, my editor, for seeing
the merit in this work. I am deeply appreciative of the dozens of researchers
who spoke to me about their work in this and related fields. Much credit is
due to the thousands of researchers who have done all the hard work of
designing and executing the research, collecting and analyzing the data that
produced the information that serves as the basis for the thoughts that I
offer in this book.
Introduction

But man is a part of nature, and his war against nature is inevitably a war
against himself.
—Rachel Carson1

The human brain is a marvelously complex organ that evolved over 250,000
years or so. During most of that period, daily life was vastly different from
our experience today. Exercising was not optional—one literally had to run
for one’s life, livelihood, and sustenance. The Stone Age diet was not a fad,
but rather the only food available. Periods of fasting arose from food scarcity,
out of necessity, and hence the earliest “keto” diet was commonplace. Life
changed greatly with the advent of agriculture, writing, government,
universities, and other institutions from ancient times to the Digital Age.
Modern life evolved exponentially from the nineteenth century onward when
industrialization, commerce, and increased urbanization wrought new types
of employment, housing, sanitation, consumer goods, and so forth. Diseases
that were previously unknown or uncommon began to surface as by-products
of civilization’s advance. Crowding and unsanitary conditions led to
epidemics such as the cholera outbreak in London’s Soho section. In original
research, a British physician, John Snow, identified the Broad Street pump as
the source of the epidemic.2 In one of the earliest applications of
epidemiology studies, he identified this source by graphing the locations of
patients stricken with the illness. While residents were skeptical of his
conclusion, as were traditionally thinking physicians who favored the miasma
theory, Snow prevailed on the authorities to remove the pump handle, and the
epidemic was ended. One could wish the current COVID-19 global pandemic
was so easy to end!
This example demonstrates that changes in ways of living can alter the
nature of illness as well as its diagnosis and treatment. Life in the twenty-first
century has undergone remarkable changes through continued mass
industrialization, the digital revolution, consumerism, climate change, growth
of medical technology and technocracy, the corporate food industry, dietary
changes, and changing cultural values. From the 1970s to the present, tens of
thousands of chemicals with a variety of applications have grown more than
forty-fold.3 These changes have impacted our bodies, especially the delicate
constituents of the brain and nervous system. This situation has led to
physical and mental discontent in new and previously unimaginable ways.
While infectious diseases still abound as the current pandemic attests, more
subtle (yet toxic) chemicals proliferate as well.
In this book, I will help elucidate some features of diseases affecting the
nervous system that are increasing in incidence and prevalence, with a focus
on those disorders that appear related to environmental toxins that modern
life has introduced. Furthermore, I will take you “behind the scenes” of the
science itself to discover the human stories involved in the discovery of these
illnesses and their treatment. I interviewed many of the leading authorities in
the fields of neuroscience, environmental toxins, integrative medicine,
neurology, geriatrics, and the microbiome (the bacteria that dwell in the
human body, especially the gut, in important equilibrium). Each of these
disciplines is quite different from the others, and yet each contributes to a
robust understanding because the complete picture is not confined to the
nervous system but involves all aspects of bodily function. When well-known
individuals are afflicted with the disorders discussed, I mention them in the
context of the illness. I also provide vignettes of selected neuroscientists and
toxicologists who have provided certain breakthroughs.
This is a voyage of discovery into the science, history, and human struggle
regarding disorders challenging the brain as well as their possible prevention.
When appropriate, I will relate them to social changes that have occurred in
our era of rapid evolution and technological growth. A subset of integrative
medicine is explored where promising aspects of research are suggesting a
way forward in dealing with these neurological disorders. I have termed this
approach, which is neither allopathic medicine nor traditional integrative
medicine, “evigrative,” for it is based on evidence from integrative and basic
research. My understanding of these challenging disorders has grown while
evaluating thousands of articles. In the course of this work, I have authored
several original medical journal articles related to this field. Coming from
outside the field of neurosciences (I was a nephrologist, physician leader in
academic general internal medicine, medical educator, clinical and health
service researcher, and bioethicist), I have been told by several
neuroscientists and environmental scientists that my perspective offers some
new insights for the field that conceivably could have some impact on
research policy as well as public health policy. I hope readers will gain
greater awareness of these illnesses and the apparent environmental and
nutritional factors contributing to them, as well as where research appears
promising to avoid such disorders. I have no financial interest in any health
products, nor am I selling any other goods or services related to them. Any
royalties from this book I will gladly donate to charity or research.
Several themes emerge in ensuing chapters that bear mentioning now:

1. Nutrition is crucially important in both the causation and the prevention of

several contemporary diseases. The role of nutritional therapy has been
seriously underutilized as a component of the efforts to combat many of
these contemporary disorders. The microbiome, or the microorganisms that
live in the human body, is a major factor to be considered, as there is a gut
microbiome–brain connection that highly impacts health and wellness.
Micronutrients, mineral and subtle vitamin deficiencies, and imbalances
are often overlooked and are factors in many disorders described here. The
education of allopathic physicians has little focus on nutrition. Nutritionists
and naturopaths may offer some insights in this regard. There are perhaps
some “low-hanging fruit” in improving American brain health through
improved nutrition, but they have little cachet in the allopathic healthcare
industry.
2. “Evigrative” medicine is a subset of integrative medicine. It derives
knowledge from a scientific investigation using biochemical, genomic, and
metabolic research as well as case studies rather than clinical trials. While
this approach has yielded new potentially important discoveries, it remains
to be seen whether they can more fully be evaluated and validated by
careful, prospective clinical trials. The obstacles to accomplishing this task
will be discussed in the subsequent pages. I am not advocating this
approach—only trying to glean what one may learn from it. While the
mind–brain interactions are rather well established, I will focus on brain–
other organ interactions as well as cellular effects of environmental toxins
and diets.
3. There are numerous toxins in the human environment as a result of our
highly industrialized way of life that need to be better accounted for to
reduce the incidence of common serious diseases. Some of these toxins
may even be medications that have short-term benefits but serious long-
term side effects. Even the ubiquitous analgesic, acetaminophen, is a
suspect in the roundup of suspected neurotoxins. Digital violence is also
considered as a potential toxin, reflecting content’s impact on brain
neuroplasticity.
4. “Eiser’s Corollary of Related Toxicity”: If a substance is toxic to the
detoxifying organs, the liver and the kidney, it is highly likely to be
neurotoxic as well. The liver and kidney serve as the two vital organs in the
body that deal with the toxins present in the environment. Neurons and
their accompanying cells (astrocytes) are among the most delicate cells in
the human body. Presently, this corollary is only a working proposition, but
there is a substantial amount of evidence suggesting this is the case. For
this reason, a chapter on liver disease is included. It is a fortuitous
inclusion based on the latest research indicating the links between the liver
and brain in health and disease are very substantial.
5. There is a tremendous amount of knowledge of environmental toxins
within schools of public health. Following in the path of John Snow
mentioned earlier, professors in these schools have systematically studied
the health impacts of environmental hazards. By contrast, physicians who
 graduate from allopathic medical schools seem less in touch with
environmental health hazards except for a small subset. Clinical interest in
these types of disorders can be found among integrative physicians. Hence
this book covers insights from the disciplines of both public health and
integrative medicine as well as neuroscience.

I reference many studies in this book, including four articles I have written
and that were published in peer-reviewed journals. “The Postmodern Stress
Disorder: A Possible New Disorder,” published in the American Journal of
Medicine in 2015, addresses the role of violent digital media in provoking
mass shootings and related events. Much of this book addresses chemical and
biological toxins in the environment and how they affect brain health. The
second article, “Why Does Finland Have the Highest Dementia Mortality
Rate? Environmental Factors May Be Generalizable,” published in the
journal Brain Research in 2017, examines factors in the Finnish environment
that may account for the unusually high rates of dementia there. These
environmental factors are present in the United States and Canada as well,
which also have high rates of dementia in international comparisons. The
third article, “Neuroplasticity, Repetitive Digital Violence, Mass Shootings
and Suicide: Toxic Content in the Digital Age,” was published in the Health
Affairs Blog in February 2019 and includes public policy suggestions to
mitigate the dangers of violent digital media usage. The fourth article is
“Prevention of Dementia: Integrative Medicine and Its Differing
Epistemology,” published in the American Journal of Medicine in print in
April 2020. An article titled “Extra-Cranial Factors in the Development of
Alzheimer’s Disease,” written with dementia expert Tamas Fulop, MD, PhD,
appeared online in Brain Research in September 2020 and established the
multisystem nature of the development of Alzheimer’s disease (AD). This
article paves the ways for new approaches to be researched regarding
preventing and treating early AD.
Environmental toxins play a subtle but significant role in
neurodegenerative disorders, and their effects impact other human organ
systems as well. The human effort to unravel these and related mechanisms
creates a compelling narrative of research and practice. Share this voyage of
discovery wherever it may lead and observe the obstacles encountered. Also
consider the social and economic factors that may influence the way forward.
Your increased awareness of the subject may lead to improved public health
policy in this regard as well as increased knowledge of preventive measures.
 1
Tempering the Inflamed Brain

Any man could, if he were so inclined, be the sculptor of his own brain.
—Santiago Ramón y Cajal

RAMON Y CAJAL AND THE BIRTH OF NEUROSCIENCE

When and how did our knowledge of neurons, astrocytes, and glial cells
begin to emerge? To ponder this evolution of knowledge, we need to turn to
a remarkable man, Santiago Ramon y Cajal, born in 1852 in Petilla de
Aragon, Navarre, Spain. Cajal was one of the first and foremost
neuroscientists in the world and is regarded as a founder of the discipline.
Not surprisingly, he was one of the first to consider the structure and
functions of neuroglial cells. Cajal was a rebellious youth frequently
expelled from school. (He probably would have been diagnosed in today’s
American schools with attention deficit hyperactivity disorder [ADHD],
were he a student here.) Later he displayed skill as an artist and gymnast,
but his father first apprenticed him to become a barber and shoemaker.1
Those efforts failed, as he was certainly ill suited to their repetitive nature.
His father had, in the meantime, become an anatomy professor at the
University of Zaragoza in Spain and encouraged Cajal to use his artistic
talents to sketch anatomical figures and remains. This task resonated with
Cajal, and he subsequently agreed to enroll in medical school there. Upon
graduation and searching for adventure and some profit, he was recruited as
a military physician. At the time, Spain was fighting the Ten Years’ War in
Cuba, putting down the rebellion there. Cajal went off to the war, during
which he contracted both tuberculosis and malaria, two life-threatening
infections. Fortunately for the future of neuroscience, he remarkably
recovered from those illnesses and, upon returning to civilian life, applied
his military bonus to the purchase of a microscope. Peering through that
scope (and another more refined one with a Zeiss lens provided by the
Spanish government), Cajal developed the contiguous neuron theory of the
nervous system. This concept holds that neurons communicate with one
another while retaining their individual distinctive cell structure. Neuronal
cells communicate with one another by forming synapses where
electrochemical events build a burgeoning “forest” of branching
communications. His sketches of the microscopic cells were crucial
evidence of his theory and were so precise they are still used to educate
neuroanatomists and physicians to this day.
Cajal originally hailed from the Aragon region of Spain, where the local
character was known for its enduring tenacity. This characteristic, along
with his meticulousness and creative imagination, was essential to his path-
breaking studies of the nervous system and a prescient understanding of
how the nervous system functions. For his efforts, he shared the 1906 Nobel
Prize in Physiology and Medicine with the Italian scientist Camille Golgi.
Golgi had developed the staining techniques that led to visualizing neurons
and other cells of the central nervous system (CNS). Cajal and Golgi had
opposing views of how the brain worked, which led to quite an interesting
Nobel awards ceremony where conflicting theories were advanced
concurrently.2 Cajal, in keeping with his rebellious character, adopted and
modified Golgi’s method of staining nerve cells that permitted him to peer
more precisely into the nervous system. He accomplished this while serving
as a professor at the University of Barcelona School of Medicine. (When in
Barcelona a few years ago, I visited the historic amphitheater where Cajal
lectured during his tenure there.)
Cajal also helped elucidate the physiological function of the astrocyte. He
was the first to note that astrocytes played an important mediating role
between neurons and the capillary blood vessels needed to maintain brain
tissue as viable.3 The local microcirculation appeared to be physically
dependent on astrocytes, and contemporary research in this area has
provided further evidence that this is the case.
Another interesting point to note is that during human evolution brain
size increased 300 percent from our ape forebears; yet this great increase
was accompanied by only a 125 percent increase in the number of neurons.
So, a greater number of astrocytes and other glial cells appear to have been
important in the development of higher intelligence.4 Cajal himself must
have possessed a great many (healthy) astrocytes to visualize how the brain
functions so clearly over a hundred years ago!
I wish to suggest that we need to learn not only the basics of
neuroscience from Cajal but also his healthy skepticism of the received
wisdom of the academic establishment. If we were merely to adopt the
conventional understanding of brain disease, we could be stuck in neutral as
our current state of treating and preventing neurological disorders such as
dementia and autism.

THE BRAIN NEEDS SUPPORT CELLS

Two hundred thousand years before the first personal computer there was
the human brain: portable, reprogrammable, waterproof, and not designed
with planned obsolescence. Somewhat prone toward errors yet still able to
get our species around saber-tooth tigers for the most part. How is it all
possible? Nearly one hundred billion individual neuronal cells intricately
wired to provide sensory inputs, analyze data, make complex computations
and plans, endure hardships, develop readjustments to skillfully use tools,
interact socially, and learn both basic and advanced survival skills. The
complex human brain requires more than neurons with their axons and
dendrites that serve as the digital relays of our computational and creative
brain. These cells that support the intricate matrix of neurons are known as
neuroglial cells. We are interested in these oft-forgotten members of the
nervous system family because of their role in defending neurons from
toxic insult, an increasing burden in these times.

BRAIN STRUCTURE, FUNCTION, AND THE BLOOD-

BRAIN BARRIER
There are three main types of glial cells: astrocytes, microglia, and
oligodendrocytes.
Astrocytes are the star-shaped support cells that have a role in
establishing the blood-brain barrier (BBB) that prevents toxic substances in
the bloodstream from reaching the neurons of the brain. These cells inhibit
the movement of large molecules into the cellular milieu of the brain. On
the other hand, small particles like metals may get past the BBB and
damage brain structures. An example is lead in the water supply of Flint,
Michigan, and many other locales across the nation. The lead contamination
in Flint in recent years represents considerable backsliding from the public
health initiative to remove lead from drinking water.5 When lead comes
across the BBB, it damages the brain including its astrocytes and neurons. It
has been known since ancient Rome that lead is damaging to humans and it
may have been a contributing factor in the fall of Rome. We are still
learning how other metals are also neurotoxic.
Astrocytes provide needed nutrients to the neurons, including glucose
and amino acids. They are also important in maintaining the balance of the
various ions, especially potassium.6 Too much potassium around neurons
can result in seizure activity (epilepsy) when neurons become overexcited
for lack of the modulating effect of astrocytes.
Another category of glial cells is the oligodendrocyte that insulates
neurons by promoting myelin along their length and around their
connections. There are diseases wherein demyelination occurs, such as
multiple sclerosis. Evidence exists that astrocytes secrete a factor that
promotes the myelinating activity of oligodendrocytes, suggesting
astrocytes have a crucial integrative function for brain function in general.7